tbuckley/cabot-search huggingface dataset:
Preliminary results from an early phase trial of in situ immunization of lymphoma with a virus likeparticle containing a TLR9 agonist combined with anti-PD1 therapy (NCT03983668).
Authors: Umar Farooq, Sabarish Ram Ayyappan, Chaobo Yin, Caitlin Lemke-Miltner, Brian J. Smith, Brian K. Link, George J. Weiner
Journal: Journal of Clinical Oncology (2022)

2639 Background: In situ immunization involves intratumoral (IT) injection of immunostimulatory agents to modify the tumor microenvironment with the goal of inducing an anti-tumor T cell response. Here, we report preliminary results of a clinical trial exploring in situ immunization with a virus like particle (VLP) combined with systemic pembrolizumab (Pembro) in lymphoma. The VLP, known as CMP-001 or vidutolimod (Vidu), is composed of the bacteriophage Qb capsid encapsulating the TLR9 agonist G10. Preclinical studies demonstrated generation of antibodies against the Qb capsid (anti-Qb) is necessary for Vidu to induce an anti-tumor response. In other cancers, early phase clinical trials of in situ immunization with Vidu, with and without systemic anti-PD1 therapy, have revealed early promising results. Methods: This trial included patients with relapsed lymphoma that have failed at least 1 line of therapy. The first dose of Vidu is given subcutaneously to stimulate anti-Qb that opsonizes the VLP. This is followed by IT Vidu administered weekly for seven doses, then at 3-week intervals. Pembro (200 mg fixed dose) is given intravenously every 3 weeks. Subjects continue treatment if they do not experience unacceptable toxicities and in the investigator’s opinion continued treatment is in the subject’s best interest. Fine needle aspirates for flow cytometric analysis are obtained prior to therapy and 4-6 weeks following initiation of therapy. Results: Six patients have enrolled to date (1 CR, 2 PR, 1 SD, 2 PD). The first 3 patients received 5mg Vidu per dose and the second cohort 7.5 mg per dose. Common side effects included chills, rigors, mild headache, and fatigue. These typically resolved within 4 hours after receiving the injection. Conclusions: In situ immunization with Vidu plus systemic anti-PD1 is a promising therapy in lymphoma. The ability to generate anti-Qb that opsonizes the VLP appears to be necessary for Vidu to induce an immune and therapeutic response. Accrual and correlative studies are continuing with the modification that generation of functional-Qb after the first dose of Vidu is required before patients receive IT therapy. Clinical trial information: NCT03983668. [Table: see text]
Survival trends among patients diagnosed with both melanoma and chronic lymphocytic leukemia.
Authors: Yayi Zhao, Rossybelle Amorrortu, Sandra C. Stewart, Kavita Ghia, Vonetta L. Williams, Vernon K. Sondak, Kenneth Yee Tsai, Javier Pinilla-Ibarz, Julio C. Chavez, Dana Elise Rollison
Journal: Journal of Clinical Oncology (2022)

e19527 Background: Patients previously diagnosed with melanoma have a higher risk of developing subsequent chronic lymphocytic leukemia (CLL). Similarly, melanoma risk has been observed to be elevated among patients with a history of CLL. However, previous studies have reported inconsistent results on whether being diagnosed with both cancers significantly reduces patient survival. Additional research is needed to assess the potential reduction in survival among this unique cohort of patients diagnosed with both melanoma and CLL. In addition, the timing of the cancer development needs to be assessed to further explore unique patient characteristics. Methods: A retrospective cohort study was conducted using data from adult patients who were diagnosed and/or treated for melanoma (n = 5,511) or chronic lymphocytic leukemia (CLL, n = 571) at Moffitt Cancer Center (MCC) in 2008-2020. Clinical characteristics and survival information were obtained from the MCC Cancer Registry including, date of diagnosis, vital status, time of death or last contact, and tumor stage at diagnosis. The Kaplan-Meier method was used to estimate survival for three patient groups: patients diagnosed with only melanoma, patients diagnosed with only CLL, and patients who were diagnosed with both cancers. The timing of the two cancer diagnoses were assessed among the 17 patients diagnosed with both melanoma and CLL. Results: The estimated 5-year survival was 78.5% and 82.9% among patients diagnosed with only melanoma and only CLL, respectively. Among patients who were diagnosed with both cancers, the 5-year survival since melanoma diagnosis was 61.4% whereas the 5-year survival since the CLL diagnosis further reduced to 60.2%. When analyzing the timing of the diagnoses of the two cancers, 13 out of 17 patients were diagnosed with melanoma prior to CLL. Further, among these 13 patients, 12 patients had CLL diagnosed within 100 days after the melanoma diagnosis. Conclusions: Patients diagnosed with both melanoma and CLL experienced poorer survival outcomes as compared to patients who were diagnosed with only one of these cancers. Among patients who were diagnosed with both cancers, more than 70% of the patients were diagnosed with CLL shortly after their melanoma diagnosis. Additional research using larger national cancer registry databases can help to advance the understanding of the underlying disease mechanism and confirm the observed timing of diagnoses is due to the CLL being diagnosed incidentally as result of node biopsies for melanoma.
The prognostic impact of intramural invasion in patients undergoing surgery for non-metastatic colon cancer.
Authors: Leyla Ozer, Elif Şenocak Taşçi, Arda Ulaş Mutlu, Betul Piyade, Nur Ramoğlu, Mırac Ajredini, Damla Gurleyik, Recep Çeçen, Sena Nur Dinçer, Turan Musevitoglu, Ayşe Sibel Erdamar Çetin, Ibrahim Yildiz, Erman Aytac
Journal: Journal of Clinical Oncology (2022)

e15516 Background: The invasion of extramural veins is an independent predictor of poor outcome in colorectal cancer whereas the significance of intramural component of venous as well as lymphatic and perineural invasion is less clear. We aimed to search the prognostic impact of these invasion patterns and their association with various clinicopathological variables. Methods: All patients undergone surgery for colon cancer between December 2014 and December 2020 were analyzed retrospectively and patients with stage II and III disease were enrolled. The patients were divided into four categories as no invasion, intramural invasion only, extramural invasion only or both (intramural and extramural) for vascular invasion (VI), lymphatic invasion (LI) and perineural invasion (PNI). 5-year disease-free (DFS) and overall-survival (OS) were the primary outcomes. Results: 626 patients were included (47.1% stage II patients). There was no significant difference between the presence of ‘intramural only’ venous (DFS, 87.2 vs 88.4% p = 0.84; OS, 88.3 vs 90.7% p = 0.90), lymphatic (DFS, 89.5 vs 85.1%, p = 0.13; OS, 89.5 vs 89.4%, p = 0.9) and perineural invasion (DFS, 89.1 vs 80.9%, p = 0.26; OS, 90.6 vs 84.8%, p = 0.12) compared to ‘no invasion’ in terms of DFS and OS. Invasion of both intramural and extramural compartments for each of these parameters demonstrated poor survival. Presence of exclusively extramural venous and perineural invasion without intramural invasion had adverse effect on DFS (87.2 vs 78.7%, p = 0.036, 89.1 vs 80.9%, p = 0.044, respectively) but not OS (88.3 vs 89.3%, p = 0.78, 90.6 vs 83.8%, p = 0.215, respectively). Tumor sidedness did not have impact on the depth and rate of lymphatic invasion however right-sided and dMMR tumors exhibited less venous and perineural invasion (24.7 vs 33.9% p = 0.007; 34.5 vs 41.5% p = 0.034 and 13.5 vs 33.5% p &lt; 0.001; 25 vs 41.4% p = 0.004, respectively). The ratio of stage III patients with venous, lymphatic and perineural invasion was consistently higher when compared with stage II patients (for LI 69.8 vs 39.7% vs p &lt; 0.001; for VI 36.9 vs 22.7% p &lt; 0.001; for PNI 51.4 vs 24.4% p &lt; 0.001). Low grade tumors exhibited less LI and PNI when compared with high grade tumors (for LI 53.2 vs. 71.3% p = 0.004, for PNI 37.1 vs. 48.3% p = 0.031) however there was no significant difference for venous invasion rates among two groups. Conclusions: Presence of merely intramural component of invasion may not be considered a synonym for lymphovascular invasion which is supposed to be a high-risk factor for systemic recurrence.
Mapping global oncology priorities: A survey of the directors of the NCI-designated cancer centers.
Authors: Laura Prakash, Taylor Estes, Elise M. Garton, Linsey Eldridge, Mishka K. Cira, Kalina Duncan, Satish Gopal, Min He, Henry Ciolino, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2022)

11008 Background: By 2040, an estimated 69% of all cancer deaths globally will occur in LMICs. Recognizing this, ASCO formed the Academic Global Oncology Task Force in 2017 to help formalize the global oncology (GO) field. Their recommendations included: better engagement with the National Cancer Institute (NCI) Center for Global Health (CGH), increased funding, and development of forums to highlight global cancer research and control activities. To further clarify how GO programs are defined and to better understand the perspectives and needs of cancer research leaders, CGH conducted a survey of the 71 Directors at the NCI-Designated Cancer Centers (NDCC). Methods: A 19-question survey was designed using Microsoft Forms and sent to the NDCC Directors via email. Responses were collected from July to September 2021. Two coders reviewed the qualitative responses to categorize the data into thematic areas. Analyses were conducted in Microsoft Excel. Results: Seventy of 71 (99%) NDCC Directors responded to the survey. 41 NDCCs (59%) reported dedicated GO programs or plans to create such a program within 5 years. Additionally, 16 Directors reported GO activities without a dedicated program, while 13 reported no GO activities. The Directors described GO as having high/extremely high (39%) or moderate (50%) importance relative to other priorities, across all types of NDCCs (basic, clinical, or comprehensive). Eight NDCCs (11%) described GO as a low priority or non-priority. 31 NDCCs (44%) reported dedicated funding for GO activities. Directors estimated interest in GO to be higher among junior faculty and trainees than senior and mid-career faculty. Future goals for established or developing GO programs included: recruitment of leadership, formalizing a strategic vision, establishing partnerships, and increasing the number of activities with international collaborations. Barriers noted were limited funding, limited capacity and expertise, and prioritizing the needs in domestic NDCC catchment areas. Conclusions: Despite variation across NDCCs, GO interest is strong as expressed by Center Directors. Strategic planning, increased funding, and improved collaboration within and between NDCCs were reported as necessary to strengthen GO at NDCCs. Continued leadership from ASCO, the NCI, and other international organizations can help facilitate dialogue and increase the prioritization of GO activities at NDCCs.
Exploring homologous recombination deficiency thresholds for predicting response to platinum-based treatment in triple negative breast cancer.
Authors: Kirsten Timms, Lauren Lenz, Elizabeth S. Cogan, Erica L. Mayer, Virginia G. Kaklamani, Vered Stearns, Vandana G Abramson, Carla Isadora Falkson, Rachel Catherine Jankowitz, P. Kelly Kelly Marcom, Nadine M. Tung, William John Gradishar, James M. Ford, Shaveta Vinayak, Judy Caroline Boughey, Matthew P. Goetz, Anna Maria Storniolo, Roisin M. Connolly, Andrea L. Richardson, Melinda L. Telli
Journal: Journal of Clinical Oncology (2022)

525 Background: Homologous recombination deficiency (HRD) status can be used to identify patients who are eligible for treatment with DNA damaging agents. Using a 3-biomarker Genomic Instability Score (GIS) threshold of ≥42, studies have previously examined the association between HRD status and outcomes in patients with triple negative breast cancer (TNBC). However, evidence suggests that a GIS threshold of ≥33 may be more appropriate. Here, we conducted an exploratory analysis evaluating the ability of ≥33 and ≥42 GIS thresholds to predict response to platinum-based treatment in patients with TNBC. Methods: Patients across 5 cohorts (TBCRC030 1 , TBCRC008 2 , NCT01372579 3 , PrECOG 0105 4 , combined cisplatin cohort 4 ) were included in this analysis if they had a primary TNBC diagnosis, received neoadjuvant platinum-based treatment, had a valid GIS, and had known pathologic complete response (pCR) status. GIS was determined by a combination of loss of heterozygosity, telomeric-allelic imbalance, and large-scale state transitions. 4,5 BRCA mutation status was defined by loss of function resulting from a pathogenic variant in BRCA1 or BRCA2. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated by comparing binary threshold status and binary pCR status. Results: A total of 204 tumors (158 BRCAwt; 33 BRCAm; 13 unknown) were included; pCR to platinum-based treatment occurred in 55 cases (39 BRCAwt; 14 BRCAm; 2 unknown). Sensitivity, specificity, PPV, and NPV were comparable between the ≥33 and ≥42 GIS thresholds, with the ≥33 threshold producing higher sensitivity values. This was true when thresholds were applied to all samples and to BRCAwt samples only (Table). Among patients who achieved pCR in response to platinum-based treatment, 5.5% of patients in the full cohort and 7.7% of those in the BRCAwt cohort had a GIS between 33-41. Conclusions: To ensure that the majority of patients likely to benefit from treatment are identified, a GIS of ≥33 may be the most appropriate threshold to predict response to platinum-based treatment in patients with TNBC; however, a prospective trial will be needed to confirm these findings. Additional studies will be important to determine whether this threshold may be appropriate to determine eligibility for other DNA-damaging agents such as PARP inhibitors. 1. Ann Oncol. 2020;31(11):1518-25 2. J Nucl Med. 2015;56(1):31-7. 3. Breast Cancer Res Treat. 2015;151(3):629-38. 4. Clin Cancer Res. 2016;22(15):3764-73. 5. Breast Cancer Res Treat. 2014;16(6):1-9. [Table: see text]
Evaluating the impact of education on clinician integration of guidelines, real-world data, and patient perspectives on gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Authors: Tariqa Ackbarali, Cindy Lovelace, Jonathan R. Strosberg, Al Bowen Benson
Journal: Journal of Clinical Oncology (2022)

e23005 Background: Targeted therapies for somatostatin receptor-positive NETs have seen significant developments in recent years. Approved and investigational somatostatin analogs for GEP-NETs are changing the treatment landscape for these cancers allowing for better management of difficult-to-treat heterogeneous tumors. To improve competence in applying these advances and to consider patient perspectives in treatment selection, an educational initiative was designed in collaboration with the Healing NET Foundation. Methods: A 1-hour CME activity was broadcast live-online in October 2021 and remains on-demand through October 2022 at OMedLive.com. The first module of the CME activity focused on real-world and quality-of-life data, and consensus guidelines related to somatostatin analogs (SSA) and peptide receptor radiotherapies (PRRT). The second module of the CME activity highlighted patient perspectives based on interviews of real patient with SSA and PRRT experience. This second section was distributed via social media through the Healing NET Foundation. Knowledge and competence questions were administered pre-, immediate post-, and 2 mos. post-activity. McNemar tests compared paired responses (pre/post &amp; pre/2 mos) with Cohen’s d for effect size. Results: As of 01/28/22, 238 clinicians have participated in the activity, 80% of whom are physicians, advanced practitioners (NP/PA), and nurses. Through social distribution, the patient perspectives were viewed by 300 patients/caregivers. Across the four CME test questions low baseline knowledge/competence was observed when selecting treatment with SSA based on reported progression-free survival and time to deterioration of quality of life from clinical trial data. Clinical considerations based on patient perspectives and prophylactic regimens with PRRT also revealed low baseline knowledge/competence. Statistically significant improvements were seen for pre/post paired responses across all four CME questions with gains ranging from 25% to 53%. The greatest challenge managing a patient with GEP-NET, was identified as adherence to treatment schedules. At 2-mos. follow-up, 90% and 95% reported improved behavioral impact on both clinical practice and patient experience/outcomes, respectively. Qualitative data including clinician write-in examples of behavioral impact and patient perspectives from the interviews will be shared. Conclusions: Assessments reveal a positive impact of live-online education on clinical practice when sharing patient perspectives in context of clinical updates. Open-ended responses to behavioral impact questions illustrated clear improvements in clinician-reported patient experience and outcomes, clinical practice management, and knowledge of SSA and PRRT for patients with GEP-NETs.
The impact of diversity, equity, and inclusion training in an independent community oncology practice.
Authors: Mark T. Fleming, Tifany Lewis, Kristina Lyons, Roshonda Poole, Christina Prillaman
Journal: Journal of Clinical Oncology (2022)

11057 Background: Historically, Diversity, Equity, and Inclusion (DEI) efforts have largely been left out of private practice medical facilities – mainly present in large academic hospital centers. Virginia Oncology Associates (VOA), a member of The US Oncology Network, is an independent community oncology and hematology practice specializing in the diagnosis and treatment of cancer and blood disorders. VOA has approximately 600 total employees consisting of physicians and clinical and non-clinical staff. In August of 2020, VOA launched an initiative to foster a culture of inclusion with the creation of its Inclusion Council (IC). Sixteen employees’, both clinical (3 physicians) and non-clinical, were chosen to participate. The council reports to VOA’s joint policy board. Methods: The council partnered with an outside organization, Virginia’s Center for Inclusive Communities, to launch a practice-wide DEI training program focusing on unconscious bias and microaggression. The training was initially planned to be in person, but due to the constraints of the COVID pandemic, the training was performed using a virtual platform. The members of IC attended three two-hour sessions while other staff members and physicians were mandated to participate in at least one training session. After completion of the sessions, a survey was sent to all employees and physicians to measure the impact of DEI training. All employees were also given the opportunity to provide additional, anonymous, written feedback. Results: Table. A total of 169 employees responded. 72% of respondents agreed or strongly agreed that the program increased awareness of unconscious bias and microaggression, 67% felt that the program helps foster a culture of inclusion in the workplace, and 66% of respondents felt that the program met expectations. Conclusions: DEI efforts are vital in all aspects of health care delivery and oncology settings. DEI training met staff expectations and positively fostered a culture of inclusion by bringing attention to unconscious bias and microaggression in a community oncology practice.[Table: see text]
Outcomes for transplant-eligible, newly diagnosed Black patients (Pts) with multiple myeloma (MM): The Levine Cancer Institute (LCI) experience.
Authors: Barry Paul, Shebli Atrash, Myra M. Robinson, Megan Jagosky, Manisha Bhutani, Cindy Varga, Mauricio Pineda-Roman, Reed N. Friend, David Foureau, Kristen Cassetta, Saad Zafar Usmani, Peter M. Voorhees
Journal: Journal of Clinical Oncology (2022)

8053 Background: Studies have revealed disparities for Black (B) pts with MM, including more advanced disease at presentation, delayed therapy with novel agents such as immunomodulatory drugs (IMIDs) and proteasome inhibitors (PIs), reduced access to autologous stem cell transplant (ASCT), and under-representation in clinical trials. However, B pts tend to be younger at diagnosis and less likely to harbor high risk disease biology, suggesting outcomes could be better relative to their White (W) counterparts. To better understand outcomes by race in the setting of more optimal treatment access, we pursued a retrospective analysis of pts treated at LCI undergoing ASCT as part of first line therapy. Methods: 255 pts (181 W pts, 74 B pts) transplanted between 3/2014 – 12/2018 were included. Analysis was restricted to pts with MM who underwent a single ASCT as part of first line therapy. Pts with &lt; 1 year of follow-up and no overall survival (OS) events were excluded. Proportions were compared between groups with Fisher’s exact tests; OS and progression free survival (PFS) were evaluated with Kaplan Meier methods and compared between groups with log-rank tests. Results: Median follow-up for B and W pts was 5.0 yrs (0.9 – 7.8 yrs) and 4.1 yrs (0.5 – 8.0 yrs). At initial presentation, median age was 59 yrs (24 – 76 yrs) and 61 yrs (35 – 78 yrs, P= 0.038), anemia was present in 81.3% and 64.6% ( P= 0.020), renal impairment in 41.3% and 33.1% ( P= 0.335), and high-risk cytogenetics [gain 1q21, t(4;14), t(14;16) or del(17p)] in 25.4% and 35.9% ( P= 0.162) of B and W pts, respectively. Median time from diagnosis to ASCT was 0.6 yrs (0.3 – 2.4 yrs) and 0.5 yrs (0.3 – 2.0 yrs) for B and W pts. 35.2% of all B pts and 43.9% of all W pts treated at LCI during the study period underwent ASCT (48.3% and 64.4% of pts ≤70 yrs of age, P= 0.002), while 63.5% and 80.1% received PI/IMID-based induction therapy ( P= 0.009) and 90.5% and 93.4% received maintenance therapy post-ASCT ( P= 0.438), respectively. Although ≥very good partial responses were achieved in fewer B pts than W pts after induction (65.8% and 80.7%,( P= 0.014), there was no difference after ASCT (95.8% and 93.9%, P= 0.759). Median PFS was 5.9 yrs (95% CI 3.4 – 6.6) and 3.6 yrs (95% CI 3.0 – 4.5) for B and W pts ( P= 0.039). Median OS trended in favor of B pts ( P= 0.163) with 5-year OS of 83.0% (95% CI 71.2% - 90.3%) and 74.2% (95% CI 65.8% - 80.9%), respectively. Conclusions: Despite disparities in optimal induction therapy, Black pts with MM who underwent frontline ASCT enjoyed better PFS relative to W pts. Optimizing access to PI/IMID-based induction therapy and ASCT will be necessary to further improve OS.